Improves Protein Metabolism Research Articles

Effect of dietary and litter amendment on ammonia concentration, immune status, serum biochemical and carcass characteristics of broiler chicken during rainy season

The experiment was conducted to evaluate the effect of sodium bisulphate in litter and protease enzyme feeding on ammonia concentration, immunity status, serum biochemical parameters and carcass traits of broiler. 240 day old Vencobb broiler chicks were randomly distributed into four treatment groups, having 3 replicates of 20 chicks each. Diets were formulated as per ICAR specifications. Control group (Tc) had no dietary and litter amendments whereas experiment groups included litter amendment with sodium bisulphate @ 25 gm/sq.ft. (Ts), dietary amendment with low protein supplemented with protease enzyme @ 15000 Prot units/Kg of feed (Tp) and both dietary and litter amendment (Tsp). The results showed a significantly (P<0.05) lower ammonia concentration in the litter treated groups Ts and Tsp as compare to control group. The immune status was also better in the litter treated groups as compare to control and Tp group. There was higher dressing percentage and breast percentage in Ts group followed by Tsp, Tp and control (Tc). The total protein level was higher in Ts group birds while, the lowest level was found in Tp group at 42 day of age. All other serum biochemical parameters were within normal physiological range and differed non-significantly. It can be concluded that treatment of litter with sodium bisulphate improved protein metabolism; carcass quality and yield significantly by reducing harmful ammonia concentration in shed associated with poor litter quality during rainy season.

What factors influence protein synthesis and degradation in critical illness?

The optimal approach to improve protein metabolism in critical illness is not yet fully defined. Here, we have summarized recent literature dealing with the main catabolic and anabolic factors influencing protein kinetics in acute hypercatabolic patients. Protein/amino acid intake levels should be adapted to type and severity of illness, keeping in mind that energy overfeeding is associated with poor outcome. A number of anticatabolic nutraceuticals and drugs have been tested in acute patients. The encouraging results have been obtained with β-hydroxy-β-methylbutyrate, omega-3 fatty acids, oxandrolone, propranolol, and metformin. Their efficacy and lack of side-effects need to be confirmed. Physical therapy, including muscle electro-stimulation, appears a very promising intervention, both effective and safe. Protein catabolism can be minimized in acute patients by adequate nutritional support, early mobilization, and, possibly, pharmacological and nutraceutical interventions. A combination of these strategies should be tested in randomized controlled trials.

Effects of glutamine and glutamate supplementation in dogs with hemorrhagic enteritis

This study evaluated the effect of glutamine and glutamate supplementation on hematological and biochemical biomarkers in dogs with clinical enteritis. Fifteen young dogs (3–10 months) with clinical enteritis were divided into two groups: group 1 (G-CON)—five animals subjected to medical treatment without supplementation and group 2 (G-GLN)—ten animals subjected to medical treatment and orally supplemented with 0.5 g/Kg per day of a glutamine and glutamate for 14 days. The following variables were measured: blood count, plasma glutamine and glutamate, total plasma protein (TPP), albumin, globulin, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglycerides. Supplementation increased the concentrations of GLN, PPT, globulin, albumin, urea, and triglycerides (P < 0.05). Erythrocyte count, hemoglobin concentration, hematocrit, red blood indices, and platelet count were not affected by supplementation. There were significant elevations in total white blood cells, neutrophils, and lymphocytes (P < 0.05) after supplementation, but other variables were not significantly different. A mixture of Gln + Glu along with drug treatment was therefore capable of producing elevations in immune cells (leukocytes and lymphocytes) and biomarkers associated with improved protein metabolism and health that favor recovery of the animals without causing damage to renal and hepatic systems.

Free Amino Acid Profile and Expression of Genes Implicated in Protein Metabolism in Skeletal Muscle of Growing Pigs Fed Low-Protein Diets Supplemented with Branched-Chain Amino Acids.

Revealing the expression patterns of genes involved in protein metabolism as affected by diets would be useful for further clarifying the importance of the balance among the branched-chain amino acids (BCAAs), which include leucine (Leu), isoleucine (Ile), and valine (Val). Therefore, we used growing pigs to explore the effects of different dietary BCAA ratios on muscle protein metabolism. The Leu:Ile:Val ratio was 1:0.51:0.63 (20% crude protein, CP), 1:1:1 (17% CP), 1:0.75:0.75 (17% CP), 1:0.51:0.63 (17% CP), and 1:0.25:0.25 (17% CP), respectively. Results showed that compared with the control group, low-protein diets with the BCAA ratio ranging from 1:0.75:0.75 to 1:0.25:0.25 elevated muscle free amino acid (AA) concentrations and AA transporter expression, significantly activated the mammalian target of rapamycin complex 1 pathway, and decreased serum urea nitrogen content and the mRNA expression of genes related to muscle protein degradation (P < 0.05). In conclusion, these results indicated that maintaining the dietary Leu:Ile:Val ratio within 1:0.25:0.25-1:0.75:0.75 in low-protein diets (17% CP) would facilitate the absorption and utilization of free AA and result in improved protein metabolism and muscle growth.

Astragalus polysaccharides decrease muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling in 5/6 nephrectomised rats

Ethnopharmacological relevanceExisting evidences suggest that Radix Astragali and its polysaccharides composition (APS) can improve muscle mass, but the mechanisms need more research. Aim of the studyIn this study, we aimed to examine the effects of APS on muscle wasting at molecular level in 5/6 nephrectomised rats. Materials and methodsWe performed 5/6 nephrectomy or sham operation in 160 6-week-old Sprague–Dawley rats, and feed animals with or without 2% APS for 155 days. After treatment, we compared the change of weight, muscle fibre, protein metabolism, pro-inflammatory factors (TNF-α, IL-15, CRP) and oxidative factors (MDA, SOD) among each group. In addition, we detected the Akt/mTOR, ubiquitin proteasome, autophagy signalling and AA transporters in vivo and in vitro. ResultsData in vivo show 2% APS could alleviate weight loss and improve protein metabolism in nephrectomised rats. The levels of serum pro-inflammatory factors and oxidative factors were restored by APS treatment. In molecular levels, APS restored Akt/mTOR, MAFbx, MuRF1, Atg7, LC3B-II/LC3B-I and SLC38A2 which changed in nephrectomised rats. Data in vitro show the optimal dose of APS is 0.2mg/mL, and SLC38A2 siRNA attenuated the effects of 0.2mg/mL APS on atrophy and autophagy. ConclusionsOur results suggested APS could improve muscle wasting through Akt/mTOR, ubiquitin proteasome and autophagy signalling, and SLC38A2 may be one of potential targets.

Effect of tocopherol and acetylsalicylic acid on the biochemical indices of blood in dioxin-exposed rats

New sources of dioxins and increased dioxin concentrations in the environment, coupled with their increased bioavailability along the food chain and accumulation in adipose tissues, contribute to various adverse long-term biological effects. The purpose of the study was to determine whether tocopherol protects the CNS by decreasing the pro-inflammatory influence of free radicals generated by TCDD; whether acetylsalicylic acid inhibits the production of inflammatory mediators; and whether the combined administration of tocopherol and acetylsalicylic acid to TCDD-exposed rats has a potential CNS-protective effect. The study included 117 rats divided into 8 groups: 75 female and 12 male Buffalo rats aged 8–10 weeks, weighing 140–160g; as well as 30 female rats aged 6 weeks and weighing 120g, which were the offspring of females from each study group. In the experiment, the following substances were used: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dosed at 5μg/kg BW and 12.5μg/kg BW, diluted in a 1% DMSO solution at the concentration of 1μg/ml; α-tocopherol acetate, dosed at 30mg/kg BW, in 0.2ml of oil solution; and acetylsalicylic acid, 50mg/kg BW, suspended in 0.5ml of starch solution, administered orally using a feeding tube. Pleurisy was induced by an injection of 0.15ml of 1% carrageenin solution. The use of tocopherol reduces the adverse effects of the inflammatory reaction induced by TCDD. Administering tocopherol improves protein metabolism by reducing protein catabolism, and raises γ-globulin fraction levels. Combined acetylsalicylic acid and tocopherol suppress catabolic processes accompanying inflammation.

Low-frequency electrical stimulation attenuates muscle atrophy in CKD--a potential treatment strategy.

Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Low-frequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-γ and IL-6) increased. Expression of the M1 macrophage marker IL-1β also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKD-induced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.

Omega-3 fatty acids and protein metabolism

The increased age observed in most countries, with the associated higher rates of chronic illnesses and cancer, and a diffuse sedentary lifestyle, will increase the number of patients with clinically relevant anabolic resistance, sarcopenia and its complications. The need for solutions to this major health issue is, therefore, pressing. The metabolic derangements and other consequences associated with sarcopenia can be slowed or even prevented by specific nutritional interventions. New evidence is available about the efficacy of omega-3 fatty acid dietary supplementation to improve protein metabolism and counteract anabolic resistance through indirect effects. Studies show that the anabolic stimuli from substrates (e.g. amino acids or proteins), hormones (e.g. insulin) and/or physical activity in skeletal muscle can be enhanced by long-term fish oil administration. The review of data from recent studies on this topic suggests that dietary omega-3 fatty acid supplementation, in association with an anabolic stimulus, could potentially provide a safe, simple and low-cost intervention to counteract anabolic resistance and sarcopenia. This intervention may contribute to prevent cachexia and disabilities. Supplementation should be given in the earlier stages of sarcopenia (e.g. precachexia). Further research should, however, be performed to better understand the mechanisms involved and the best dosage and timing of administration.

Insulin therapy improves protein metabolism in the critically ill

Critical illness, trauma and burns are associated with profound metabolic abnormalities, of which protein catabolism, hyperglycemia and insulin resistance are hallmarks of these conditions. Increased protein breakdown and loss results in muscle wasting, weakness and diminished functioning. Interestingly, hyperglycemia and insulin resistance augment catabolic responses. Insulin, which is routinely administered to critically ill patients to prevent excessive hyperglycemia, also stimulates protein synthesis and prevents whole-body protein loss. The present commentary highlights the results of a recent study published in Critical Care and discusses whether moderate insulin therapy is equally as beneficial as conventional insulin therapy in preventing protein catabolism and loss.

Study of enteral nutrition on patients with severe tetanus

Objective To study the effect of enteral nutrition on patients with severe tetanus. Methods The patients totaled 60 cases were divided into two groups with 30 cases in each. The patients in EN group were treated with enteral nutrition on basis of routine treatment, control group was treated with total parenteral nutrition (TPN). The indicators values of BMI, TSF, MAMC, TP, PAm, m, ALB and Hb were tested on the day before nutrition supports and after nutrition supports 10 days later in two groups. Adverse reaction and the treatment effect were observed simultaneously. Results With nutritional supports 10 days later, two groups had no obvious decline in BMI, TSF and MAMC. TP, PA, ALB and Hb of EN group were higher than those of control group (P＜0.05) . Complication rate of EN group was lower than that of control group, there was significant differences (P＜0.05) . Conclusions Early EN may improve protein metabo lism in patients with severe tetanus and nutritional status. Key words: Severe tetanus; Enteral nutrition; Total parenteral nutrition; Nutritional support

Oxidative Stress and Aminopeptidases in Parkinson’s Disease Patients with and without Treatment

Background/Objective: Mitochondrial dysfunction, oxidative stress and protein metabolism impairment are the main molecular events underlying the pathogenesis of Parkinson’s disease (PD). However, only few studies have addressed the changes produced by these phenomena in the blood of PD patients. Our purpose was to compare oxidative stress between newly diagnosed PD patients (ntPD) and PD patients under treatment (tPD). We also analyzed changes in plasma activity of several aminopeptidases (AP) involved in the metabolism of various active peptides.Methods: Plasma lipid peroxide (LPO) and lactate (LAC) concentrations were measured by colorimetric methods, and plasma AP activities were determined by fluorometric assay. Results: LPO and LAC concentrations were significantly elevated in ntPD and tPD patients versus controls, but there were no differences between the PD groups. Alanine-, cystine- and aspartate-AP activities were significantly lower in tPD versus ntPD patients. Nondenaturing electrophoresis and Western blot results confirmed these findings. Conclusions: The plasma LPO and LAC levels were high in both PD groups, indicating that they are elevated at an early stage of PD and are not affected by anti-PD treatment. The higher AP activities in ntPD versus tPD patients suggest that anti-PD treatment may improve protein metabolism while not altering oxidative stress. A therapy directed to reduce oxidative stress and normalize AP activity may be useful in the treatment of PD.

Nutrition Support With Glutamine Dipeptide in Patients Undergoing Liver Transplantation

Aim The effect of total parenteral nutrition (TPN) support supplemented with alanyl-glutamine (Ala-Gln) dipeptide was investigated in a randomized, controlled clinical trial. Methods Sixty-five patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma admitted for orthotopic liver transplantation were randomly divided into 3 groups: diet group ( n = 21), TPN group ( n = 22), and Gln group ( n = 22). Patients in the TPN and Gln groups received isocaloric and isonitrogenous TPN for 7 days. Venous heparin blood samples were obtained for assay on days 2 and 9 after surgery; we performed routine pathologic tests. Results Compared with the results on day 9 in the TPN group, there was a significant increase in the prognostic nutrition index and in prealbumin among the Gln group. Aspartate aminotransferase improved significantly by Gln treatment compared with traditional TPN support ( P < .05). The pathologic results also showed Gln supplementation to reduce hepatic cell injury. A significant decrease in postoperative hospital stay was observed in the Gln group. Conclusions Posttransplant TPN support greatly improved protein metabolism and nutritional state of patients. TPN with Ala-Gln helped to improve synthetic function and to reduce the injury to a transplanted liver.

Long‐chain n‐3 fatty acids – New anabolic compounds improving protein metabolism

Previous animal studies demonstrated that chronic feeding of long‐chain n‐3 polyunsaturated fatty acids (LCn‐3PUFA) that modifies muscle membrane fatty acid composition promotes protein anabolism by blunting the age‐associated deterioration in insulin sensitivity. The current study assessed, as a proof of concept, the anabolic effects of LCn‐3PUFA‐rich menhaden oil in 78 male castrated pigs (20 kg initial body weight). Pigs were fed for 76 days diets containing 0, 3, or 4% menhaden oil using iso‐energetic oil substitutions in diets typical of swine production (6% fat matter). Performance and body composition were measured using ultrasound technology during growth at 55 and 85 kg according to a complete block design. Menhaden oil feeding linearly reduced feed intake with a decline from 2.58 to 2.51 kg/d (‐3%; P=0.04) at 85 kg body weight without altering body weight gain. Back fat thickness remained unchanged (11.16 mm) between treatments. The diameter of the longissimus dorsi was linearly increased as menhaden oil amount increased (50.0, 50.1, 51.8 mm; P=0.02). The results demonstrate for the first time that LCn‐3PUFA promote muscle protein accretion, this approach could be a novel intervention to ameliorate the age‐related loss of muscle mass in the human.

Dialysate as food as an option for automated peritoneal dialysis.

Protein-energy malnutrition is frequently found in dialysis patients. Many factors play a role in its development including deficient nutrient intake as a result of anorexia. Peritoneal dialysis (PD) solutions containing a mixture of amino acids and glucose in an appropriate ratio could serve as a source of food. The authors of this article found that such a dialysis solution when administered to fasting patients who were on nightly automated peritoneal dialysis (APD), as part of a regular dialysis schedule, induced an acute anabolic effect. Also in PD patients in the fed state, dialysis solutions containing both amino acids and glucose were found to improve protein metabolism. It appears that the body responds similar to intraperitoneal and oral amino acid:dialysate as food. Like dietary proteins, intraperitoneal amino acids can bring about generation of hydrogen ions and urea as a result of oxidation. No rise of serum urea levels was found and serum bicarbonate remained within the normal range when a total buffer concentration of 40 mmol/L in the mixture was used. The use of this approach may be an option for PD patients who cannot fulfil dietary recommendations.

Aspects of Protein and Amino Acid Metabolism in a Model of Severe Glutamine Deficiency in Sepsis

Background/Aims: Growth hormone (GH) could have the potential to improve protein metabolism in sepsis but glutamine deficiency has been reported after GH treatment. The aim was to investigate the effects of glutamine deficiency in sepsis with and without GH treatment on protein and amino acid metabolism. Methods: Cecal ligation and puncture (CLP) was used as a model of sepsis. Serious glutamine deficiency was induced by administration of glutamine synthetase inhibitor, methionine sulfoximine (MSO). Young Wistar rats were divided into 5 groups: control; CLP; CLP+MSO; CLP+GH, and CLP+MSO+GH. Parameters of protein metabolism were measured on incubated soleus and extensor digitorum longus muscles: [1-¹⁴C]leucine was used to estimate protein synthesis and leucine oxidation, tyrosine release was used to evaluate protein breakdown. Amino acid concentrations in plasma, skeletal muscle and incubation media were measured by HPLC. Results/Conclusions: A reduced muscle glutamine concentration after MSO treatment is not associated with changes in the rates of protein synthesis or breakdown. MSO treatment decreased glutamine release from skeletal muscle and plasma glutamine concentration. Severe glutamine deficiency in GH-treated septic rats resulted in increased release of branched-chain amino acids from skeletal muscle.

Carnitine and hemodialysis

Carnitine, gamma-trimethyl-beta-hydroxybutyrobetaine, is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in the beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and particularly by the loss through dialytic membranes, leading in some patients to carnitine depletion with a relative increase of esterified forms. The authors found a decrease in plasma-triglyceride and increase of high-density lipoprotein cholesterol (HDL-Chol) in dialysis patients during carnitine treatment. Many studies have shown that l-carnitine supplementation leads to improvements in several complications seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia, normalizing the reduced carnitine palmitoyl transferase activity in red cells. In addition, carnitine supplementation may improve protein metabolism and insulin resistance. Recently, carnitine supplementation has been approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Regular carnitine supplementation in hemodialysis patients can improve their lipid metabolism, protein nutrition, antioxidant status, and anemia requiring large doses of erythropoietin, It also may reduce the incidence of intradialytic muscle cramps, hypotension, asthenia, muscle weakness, and cardiomyopathy. Am J Kidney Dis 41(S1):S116-S122. © 2003 by the National Kidney Foundation, Inc.

α-ketoglutarate–supplemented enteral nutrition: effects on postoperative nitrogen balance and muscle catabolism

Objective Enteral feeding in the early postoperative phase may improve gut integrity and reduce infectious complications after trauma and surgery. The aim of the current study was to evaluate the feasibility of α-ketoglutarate enrichment of enteral feeding and the effect on protein metabolism after major surgery. Methods Patients undergoing elective abdominal surgery were randomly allocated to receive a standard whole-protein–based enteral nutrition solution ( n = 9) or an isonitrogenous, isocaloric solution enriched with α-ketoglutarate ( n = 11) for 5 d postoperatively. The nutritional goals by day 4 were 25 kcal and 0.17 g of nitrogen, respectively, per kilogram of body weight every 24 h. Standard blood analysis, including prealbumin and C-peptide, was performed preoperatively and on days 1, 3, and 6. Urine was collected daily for nitrogen and 3-methylhistidine analyses. Results Due to restricted tolerance to enteral feeding, the nitrogen delivery reached only 0.10 g of nitrogen per kilogram of body weight. Transthyretin decreased by 25% in both groups, and albumin decreased significantly in the enriched group compared with the standard nutrition. There were no significant differences in nitrogen balance, excretion of 3-methylhistidine, or clinical outcome between groups. Conclusions Enrichment of a whole-protein–based formula with α-ketoglutarate did not improve protein metabolism or decrease muscle catabolism after major abdominal surgery.

L-Arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia

Accumulating evidence suggests that L-arginine, under conditions of septicemia, not only enhances immune function but also improves protein metabolism. Because the effect of L-arginine administration on the protein metabolism of different organs is unknown, the aim of the study was to elucidate the effects of exogenous supplementation of L-arginine during endotoxemia on the in vivo protein metabolism of individual organs and at the whole-body level. Female pigs were cannulated with catheters in the aorta and the splenic, caval, portal, hepatic, and renal veins, enabling measurements across the hindquarter, portal-drained viscera, liver, and kidneys. Endotoxemia was induced by a 24-h continuous intravenous infusion of endotoxin (3 microg x kg body wt(-1) x h(-1)). At 8 h, an intravenous infusion of L-arginine was started (n = 8). Control pigs (n = 6) received L-alanine. At 24 h, blood was sampled. After cessation of the endotoxin infusion, L-arginine and L-alanine infusions were continued as a supplement in the enterally infused diet. At 48 h, blood samples were obtained during the postendotoxemic and nutritionally supported conditions. Stable isotopes were used to assess protein metabolism and phenylalanine hydroxylation. Both during and after the endotoxin challenge, L-arginine administration enhanced protein synthesis and degradation across the hindquarter and simultaneously reduced protein synthesis and degradation in the liver at equal rates. Protein turnover across the kidneys and portal-drained viscera remained unaffected. After endotoxemia, L-arginine infusion decreased whole-body protein turnover without affecting the net protein balance. L-Arginine administration affects protein turnover of the muscle area and the liver oppositely.

Nutritional intervention high in vitamins, protein, amino acids, and omega3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury.

Characteristic of the hypermetabolic response to a thermal injury is the massive protein catabolism and compromised structure and function of essential organs. Nutrition has been suggested to affect protein metabolism and clinical outcome after a severe injury but published studies show controversial data. The purpose of this study was to determine the effect of enriched nutritional support during the postburn hypermetabolic state on protein metabolism in serum, liver, muscle, and skin. Laboratory. Twenty-two rats were given burns covering 60% of their total body surface area and randomized to receive either standard rat chow (control) or a diet high in vitamins, protein, amino acids, and omega3 fatty acids. Five weeks after injury, body weight, serum, muscle, and hepatic protein content, insulin-like growth factor I concentration, and wound healing (reepithelization) were determined. Rats receiving the enriched diet showed a gradual improvement in body weight 1, 2, 3, 4, and 5 weeks postburn compared with controls (P< .001). Diet-fed rats demonstrated higher protein and insulin-like growth factor 1 content in serum, muscle, and liver 5 weeks after trauma (P< .001). Serum protein, albumin, and transferrin levels were significantly increased in rats receiving the diet compared with control rats (P< .001). Reepithelization was accelerated in rats receiving the enriched diet 4 (diet-fed, mean +/- SD, 23% +/- 1% vs controls, 17% +/- 1%; P< .001) and 5 (diet-fed, 24% +/- 1% vs controls, 18% +/- 1%; P< .001) weeks postburn compared with control rats. Nutritional intervention high in protein, vitamins, amino acids, and omega3 fatty acids improves protein net balance during the hypermetabolic response to thermal injury. Compromised organ function and structure and clinical outcome during the hypermetabolic response may be improved.

Glutamine supplementation in cancer patients

OBJECTIVES: Three series of studies investigated whether 1) glutamine deficiency occurs in tumor-bearing rats, 2) glutamine supplementation improves protein metabolism during chemotherapy in tumor-bearing rats, and 3) oral glutamine supplement improves systemic immune and gut-barrier function in patients with esophageal cancer receiving radiochemotherapy.METHODS: In the animal studies, AH109A hepatoma cells or Yoshida sarcoma cells were inoculated into male Donryu rats to induce tumors. Glutamine production was measured by U-14C-glutamine infusion and the conversion of arginine to glutamine was measured by infusion of U-14C-arginine. The effect of glutamine on protein metabolism was investigated by 1-14C-leucine infusion. In the clinical study, 13 patients with esophageal cancer were randomized into two groups, control and glutamine supplemented (30 g/d), for 4 wk.RESULTS: Glutamine levels in plasma and skeletal muscle were decreased in tumor-bearing rats, although glutamine production and the conversion of arginine to glutamine were increased. Glutamine-supplemented total parenteral nutrition reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing rats. Oral supplementation of glutamine to the patients with esophageal cancer enhanced lymphocyte mitogenic function and reduced permeability of the gut during radiochemotherapy.CONCLUSIONS: Glutamine depletion in host tissues occurs in tumor-bearing rats. Glutamine supplementation can attenuate loss of protein in the muscle in tumor-bearing animals and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer.